Skip to main content
PMC home page
The Journal of Physiology logoLink to The Journal of Physiology
. 1995 Sep 1;487(Pt 2):359–366. doi: 10.1113/jphysiol.1995.sp020885

Receptor kinase-dependent desensitization of the muscarinic K+ current in rat atrial cells.

Z Shui 1, M R Boyett 1, W J Zang 1, T Haga 1, K Kameyama 1
PMCID: PMC1156578  PMID: 8558469

Abstract

1. Activity of rat atrial muscarinic K+ channels has been measured in five configurations of the patch clamp technique. 2. In configurations in which the normal intracellular solution was lost, the slow phase of desensitization (a slow decline of channel activity during an exposure to ACh) was much reduced (or absent) and deactivation (on wash-off of ACh) was slowed as compared with desensitization and deactivation in configurations in which normal intracellular solution was retained. This suggests that soluble intracellular regulators are involved in these processes. 3. When a G protein-coupled receptor kinase (GRK2) was applied to the cytoplasmic surface of conventional outside-out patches in the presence of ATP, the slow phase of desensitization was restored. In the absence of ATP, GRK2 failed to restore the slow phase. 4. It is concluded that (i) G protein-coupled receptor kinase dependent phosphorylation of the muscarinic receptor is responsible for the slow phase of desensitization and (ii) a soluble factor (such as a GTPase activating protein or 'GAP') is responsible for normal rapid deactivation.

Full text

PDF
359

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Benovic J. L., DeBlasi A., Stone W. C., Caron M. G., Lefkowitz R. J. Beta-adrenergic receptor kinase: primary structure delineates a multigene family. Science. 1989 Oct 13;246(4927):235–240. doi: 10.1126/science.2552582. [DOI] [PubMed] [Google Scholar]
  2. Bourne H. R., Stryer L. G proteins. The target sets the tempo. Nature. 1992 Aug 13;358(6387):541–543. doi: 10.1038/358541a0. [DOI] [PubMed] [Google Scholar]
  3. Boyett M. R., Kirby M. S., Orchard C. H., Roberts A. The negative inotropic effect of acetylcholine on ferret ventricular myocardium. J Physiol. 1988 Oct;404:613–635. doi: 10.1113/jphysiol.1988.sp017309. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Haga T., Haga K., Kameyama K. G protein--coupled receptor kinases. J Neurochem. 1994 Aug;63(2):400–412. doi: 10.1046/j.1471-4159.1994.63020400.x. [DOI] [PubMed] [Google Scholar]
  5. Harrison S. M., McCall E., Boyett M. R. The relationship between contraction and intracellular sodium in rat and guinea-pig ventricular myocytes. J Physiol. 1992 Apr;449:517–550. doi: 10.1113/jphysiol.1992.sp019100. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Higashijima T., Ferguson K. M., Smigel M. D., Gilman A. G. The effect of GTP and Mg2+ on the GTPase activity and the fluorescent properties of Go. J Biol Chem. 1987 Jan 15;262(2):757–761. [PubMed] [Google Scholar]
  7. Honjo H., Kodama I., Zang W. J., Boyett M. R. Desensitization to acetylcholine in single sinoatrial node cells isolated from rabbit hearts. Am J Physiol. 1992 Dec;263(6 Pt 2):H1779–H1789. doi: 10.1152/ajpheart.1992.263.6.H1779. [DOI] [PubMed] [Google Scholar]
  8. Kaibara M., Nakajima T., Irisawa H., Giles W. Regulation of spontaneous opening of muscarinic K+ channels in rabbit atrium. J Physiol. 1991 Feb;433:589–613. doi: 10.1113/jphysiol.1991.sp018445. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Kameyama K., Haga K., Haga T., Kontani K., Katada T., Fukada Y. Activation by G protein beta gamma subunits of beta-adrenergic and muscarinic receptor kinase. J Biol Chem. 1993 Apr 15;268(11):7753–7758. [PubMed] [Google Scholar]
  10. Kameyama K., Haga K., Haga T., Moro O., Sadée W. Activation of a GTP-binding protein and a GTP-binding-protein-coupled receptor kinase (beta-adrenergic-receptor kinase-1) by a muscarinic receptor m2 mutant lacking phosphorylation sites. Eur J Biochem. 1994 Dec 1;226(2):267–276. doi: 10.1111/j.1432-1033.1994.tb20050.x. [DOI] [PubMed] [Google Scholar]
  11. Kim D. Modulation of acetylcholine-activated K+ channel function in rat atrial cells by phosphorylation. J Physiol. 1991 Jun;437:133–155. doi: 10.1113/jphysiol.1991.sp018588. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Kurachi Y., Nakajima T., Sugimoto T. Short-term desensitization of muscarinic K+ channel current in isolated atrial myocytes and possible role of GTP-binding proteins. Pflugers Arch. 1987 Oct;410(3):227–233. doi: 10.1007/BF00580270. [DOI] [PubMed] [Google Scholar]
  13. Kwatra M. M., Leung E., Maan A. C., McMahon K. K., Ptasienski J., Green R. D., Hosey M. M. Correlation of agonist-induced phosphorylation of chick heart muscarinic receptors with receptor desensitization. J Biol Chem. 1987 Dec 5;262(34):16314–16321. [PubMed] [Google Scholar]
  14. Pitcher J. A., Inglese J., Higgins J. B., Arriza J. L., Casey P. J., Kim C., Benovic J. L., Kwatra M. M., Caron M. G., Lefkowitz R. J. Role of beta gamma subunits of G proteins in targeting the beta-adrenergic receptor kinase to membrane-bound receptors. Science. 1992 Aug 28;257(5074):1264–1267. doi: 10.1126/science.1325672. [DOI] [PubMed] [Google Scholar]
  15. Rae J., Cooper K., Gates P., Watsky M. Low access resistance perforated patch recordings using amphotericin B. J Neurosci Methods. 1991 Mar;37(1):15–26. doi: 10.1016/0165-0270(91)90017-t. [DOI] [PubMed] [Google Scholar]
  16. Reuveny E., Slesinger P. A., Inglese J., Morales J. M., Iñiguez-Lluhi J. A., Lefkowitz R. J., Bourne H. R., Jan Y. N., Jan L. Y. Activation of the cloned muscarinic potassium channel by G protein beta gamma subunits. Nature. 1994 Jul 14;370(6485):143–146. doi: 10.1038/370143a0. [DOI] [PubMed] [Google Scholar]
  17. Sakmann B., Noma A., Trautwein W. Acetylcholine activation of single muscarinic K+ channels in isolated pacemaker cells of the mammalian heart. Nature. 1983 May 19;303(5914):250–253. doi: 10.1038/303250a0. [DOI] [PubMed] [Google Scholar]
  18. Tsuga H., Kameyama K., Haga T., Kurose H., Nagao T. Sequestration of muscarinic acetylcholine receptor m2 subtypes. Facilitation by G protein-coupled receptor kinase (GRK2) and attenuation by a dominant-negative mutant of GRK2. J Biol Chem. 1994 Dec 23;269(51):32522–32527. [PubMed] [Google Scholar]
  19. Zang W. J., Yu X. J., Honjo H., Kirby M. S., Boyett M. R. On the role of G protein activation and phosphorylation in desensitization to acetylcholine in guinea-pig atrial cells. J Physiol. 1993 May;464:649–679. doi: 10.1113/jphysiol.1993.sp019656. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from The Journal of Physiology are provided here courtesy of The Physiological Society

RESOURCES